This research project is designed to investigate a proposed role for the "active" form of orosomucoid (alpha1-acid glycoprotein) as a cofactor in the lipoprotein lipase reaction. Large quantities of urine from nephrotic patient were processed to obtain sufficient starting material. New techniques were developed for investigating the nature of the carbohydrate containing compounds in urine from nephrotic patients and normal subjects. The lipoprotein lipase activator has now been identified as a low molecular weight form of heparan sulfate which is excreted in the free from in normal subjects and as a complex with orosomucoid in nephrotic patients. Urinary heparan sulfate is twice as effective as heparin in stimulating the triglyceride hydrolase reaction. A new proteoglycan has been identified in urine from nephrotic patients. It is approximately 50% protein and 50% glycosaminoglycan and is quite resistant to degradation. Preliminary evidence suggest that it may contain sulfate and may function in plasma as a precursor to free heparan sulfate. Quantitation of these compounds in plasma is now under study. The mechanism of action of the urinary heparan sulfate in vivo and in vitro will be investigated.